Lin Lu1, Deling Wang2, Lili Wang3, Linning E4, Pingzhen Guo1, Zhiming Li5, Jin Xiang6, Hao Yang1, Hui Li2, Shaohan Yin2, Lawrence H Schwartz1, Chuanmiao Xie7, Binsheng Zhao8. 1. Department of Radiology, Columbia University Medical Center, 710 West 168th Street, B26, New York, NY, 10032, USA. 2. Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. 3. Department of Molecular Pathology, the Affiliated Hospital of Qingdao University, Qingdao University, Wutaishan Road 1677, Qingdao, 266000, Shandong, People's Republic of China. 4. Department of Radiology, Shanxi BETHUNE Hospital, 99 Longcheng Street, Taiyuan, 030032, Shanxi, People's Republic of China. 5. Department of Radiology, the Affiliated Hospital of Qingdao University, Qingdao University, Wutaishan Road 1677, Qingdao, 266000, Shandong, People's Republic of China. 6. Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. 7. Department of Radiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China. xchuanm@sysucc.org.cn. 8. Department of Radiology, Columbia University Medical Center, 710 West 168th Street, B26, New York, NY, 10032, USA. bz2166@cumc.columbia.edu.
Abstract
OBJECTIVES: Classification of histologic subgroups has significant prognostic value for lung adenocarcinoma patients who undergo surgical resection. However, clinical histopathology assessment is generally performed on only a small portion of the overall tumor from biopsy or surgery. Our objective is to identify a noninvasive quantitative imaging biomarker (QIB) for the classification of histologic subgroups in lung adenocarcinoma patients. METHODS: We retrospectively collected and reviewed 1313 CT scans of patients with resected lung adenocarcinomas from two geographically distant institutions who were seen between January 2014 and October 2017. Three study cohorts, the training, internal validation, and external validation cohorts, were created, within which lung adenocarcinomas were divided into two disease-free-survival (DFS)-associated histologic subgroups, the mid/poor and good DFS groups. A comprehensive machine learning- and deep learning-based analytical system was adopted to identify reproducible QIBs and help to understand QIBs' significance. RESULTS: Intensity-Skewness, a QIB quantifying tumor density distribution, was identified as the optimal biomarker for predicting histologic subgroups. Intensity-Skewness achieved high AUCs (95% CI) of 0.849(0.813,0.881), 0.820(0.781,0.856) and 0.863(0.827,0.895) on the training, internal validation, and external validation cohorts, respectively. A criterion of Intensity-Skewness ≤ 1.5, which indicated high tumor density, showed high specificity of 96% (sensitivity 46%) and 99% (sensitivity 53%) on predicting the mid/poor DFS group in the training and external validation cohorts, respectively. CONCLUSIONS: A QIB derived from routinely acquired CT was able to predict lung adenocarcinoma histologic subgroups, providing a noninvasive method that could potentially benefit personalized treatment decision-making for lung cancer patients. KEY POINTS: • A noninvasive imaging biomarker, Intensity-Skewness, which described the distortion of pixel-intensity distribution within lesions on CT images, was identified as a biomarker to predict disease-free-survival-associated histologic subgroups in lung adenocarcinoma. • An Intensity-Skewness of ≤ 1.5 has high specificity in predicting the mid/poor disease-free survival histologic patient group in both the training cohort and the external validation cohort. • The Intensity-Skewness is a feature that can be automatically computed with high reproducibility and robustness.
OBJECTIVES: Classification of histologic subgroups has significant prognostic value for lung adenocarcinoma patients who undergo surgical resection. However, clinical histopathology assessment is generally performed on only a small portion of the overall tumor from biopsy or surgery. Our objective is to identify a noninvasive quantitative imaging biomarker (QIB) for the classification of histologic subgroups in lung adenocarcinoma patients. METHODS: We retrospectively collected and reviewed 1313 CT scans of patients with resected lung adenocarcinomas from two geographically distant institutions who were seen between January 2014 and October 2017. Three study cohorts, the training, internal validation, and external validation cohorts, were created, within which lung adenocarcinomas were divided into two disease-free-survival (DFS)-associated histologic subgroups, the mid/poor and good DFS groups. A comprehensive machine learning- and deep learning-based analytical system was adopted to identify reproducible QIBs and help to understand QIBs' significance. RESULTS: Intensity-Skewness, a QIB quantifying tumor density distribution, was identified as the optimal biomarker for predicting histologic subgroups. Intensity-Skewness achieved high AUCs (95% CI) of 0.849(0.813,0.881), 0.820(0.781,0.856) and 0.863(0.827,0.895) on the training, internal validation, and external validation cohorts, respectively. A criterion of Intensity-Skewness ≤ 1.5, which indicated high tumor density, showed high specificity of 96% (sensitivity 46%) and 99% (sensitivity 53%) on predicting the mid/poor DFS group in the training and external validation cohorts, respectively. CONCLUSIONS: A QIB derived from routinely acquired CT was able to predict lung adenocarcinoma histologic subgroups, providing a noninvasive method that could potentially benefit personalized treatment decision-making for lung cancer patients. KEY POINTS: • A noninvasive imaging biomarker, Intensity-Skewness, which described the distortion of pixel-intensity distribution within lesions on CT images, was identified as a biomarker to predict disease-free-survival-associated histologic subgroups in lung adenocarcinoma. • An Intensity-Skewness of ≤ 1.5 has high specificity in predicting the mid/poor disease-free survival histologic patient group in both the training cohort and the external validation cohort. • The Intensity-Skewness is a feature that can be automatically computed with high reproducibility and robustness.
Entities:
Keywords:
Adenocarcinoma of lung; Deep learning; Histological types of neoplasms; Machine learning; Tomography, X-ray computed
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